Amine-boranes as bifunctional reagents for direct amidation of carboxylic acids

A process for direct activation and subsequent amidation of an aliphatic or an aromatic carboxylic acid to manufacture an amide R3CONR1R2, comprising the steps of

• a. preparing an amine-borane R1R2NH—BH3 from an amine R1R2NH;
• wherein R1 and R2 are, independently, hydrogen, an alkyl, or an aryl, wherein said alkyl or aryl are optionally substituted and said R1 and R2 are not both an aryl or a hydrogen at the same time;
• b. preparing a carboxylic acid R3COOH, wherein R3 is an alkyl or an aryl, each of which is optionally substituted;
• c. dissolving one equivalent of said amine-borane and about three equivalents of said carboxylic acid in xylenes or a compatible solvent to afford a reaction mixture;
• d. first heating said reaction mixture to about 90-100° C. for about 1 hour, then raising the temperature to about 150° C. for about 12 hours;
• and
• e. resolving said reaction mixture to afford said amide R3CONR1R2 together with recovered excess carboxylic acid R3COOH.